Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J(ss)) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2054 and Duro-Tak 2516 showed the highest J(ss) of 1.95 microg cm(-2) h(-1) and the lowest J(ss) of 1.43 microg cm(-2) h(-1), respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and the lowest enhancement ratios (ER) of the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA as measured by the 180 degrees peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that propylene glycol as a CPE and cosolvent in 10% (m/m) with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.